3-aminoalkyl-1,3-benzodiazepin-2-ones



United States Patent 3,474,094) 3AMINOALKYL-1,3-BENZGDlAZEPlN-2-ONEWilliam Blythe Wright, in, Woodclitf Lake, Ni, assignor to Americantiyanamid Company, Stamford, (301111., a

corporation of Maine No Drawing. Filed Dec. 22, 1966, Ser. No. 603,769lint. (11. $0764 53/04;A61k 27/00 US. Cl. 26l}239.3 Claims ABSTRACT (3FTHE DTSCLGSURE The preparation of substituted3-aminoalkyl-1,3-benzodiazepin-Z-ones is described. These compounds canbe prepared for example, by ring closure of a substitutedN-(O-arninophenethyl-N,N-dialkyla1kylenediamine withN,N-carbonyldiimidazole, phosgene or the like. The substituted3-aminoalkyl-1,3-benzodiazepin-2-ones are useful for theirantidepressant, hypnotic and muscle relaxant properties.

This invention relates to new organic compounds. More particularly, itrelates to 3-aminoalkyl-1,3-benzodiazepin- 2-ones and methods ofpreparing the same.

The novel compounds of the present invention have the followingstructure:

Ra R wherein R and R are selected from the group consisting of hydrogen,halogen, lower alkyl, lower alkoxy, and trifiuoromethyl; R is selectedfrom the group consisting of hydrogen and lower alkyl; n is an integer2, 3 or 4; and R and R selected from the group consisting of hydrogen,lower alkyl, cycloalkyl, aralkyl, (lower cycloalkyl)methyl, and whenNR3R4 is taken together, 1- pyrrolidinyl, lower alkyl-l-pyrrolidinyl,piperidino, lower alkylpiperidino, 4-phenylpiperidino,4-halophenylpiperidino, morpholino, lower alkylrnorpholino,hexarnethyleneimino, l-piperazinyl, 4-lower alkyl-l-piperazinyl, 4-benzyl-l-piperazinyl, 4-phenyl-1-piperazinyl, 4-(lower alkoxyphenyl)l-piperazinyl, 4-trifluoromethylpheny1-1- piperazinyl, 4-(loweralkylphenyl)-1-piperazinyl, 4-halophenyl 1 piperazinyl,3,6-dihydro-4-phenyl-1(2H)- pyridyl,4-alkylphenyl-3,6-dihydro-1(2H)-pyridyl, 3,6-dihydro-4-halophenyl-l(2H)-pyridyl, and azabicyclo-[3.2.2] nonan-3-yl; and acid addition saltsthereof.

The compounds of the present invention may be solids or liquids at roomtemperature as their free bases. As such, they are relatively insolublein water but are soluble in or miscible with most organic solvents suchas, for example, lower alkyl alcohols, esters, acetone, chloroform andthe like. These compounds form acid addition salts with strong acidssuch as hydrochloric acid, sulfuric acid, perchloric and the like. Thesesalts are, in general, soluble in water, methanol, ethanol, etc., butrelatively insoluble in benzene, ether, petroleum-ether and the like.

The compounds of this invention may be prepared by the following methodwhich has been found most desirable.

ice

wherein R, R R R R and n are as defined hereinbefore. When (A) isconverted to an acid chloride, an anhydride, an ester or anacylimidazole and then reacted with an aminoalkylamine, (B) is obtained.The nitro group in (B) can be converted to an amino group (C) by one ofthe usual literature procedures, i.e., catalytically, stannous chloride,calcium chloride in ethanol and the like. The amide group in (C) isreduced by such reagents as lithium aluminum hydride or diborane, andcompound (D) results. When (D) is reacted with such reagents asN,N-carbonyl diimidazole, phosgene and the like, (E) results. Ifdesired, (E) can be converted to (F) by alkylation, preferably in thepresence of a condensing agent such as sodium, sodium hydride, orsodamide.

An alkyl group may be introduced at the 1-position at an earlier stage,for example, as described below.

NHR2

A further method of preparing compounds of this invention is by thealkylation of a l,3-benzodiazepine2-one which contains a hydrogen atomin the 3-position.

R2 R I wherein R, R R R R and n are as previously defined and X is ahalogen or arylsulfonyloxy group. Suitable solvents for this reactionare benzene, toluene, ethanol, tetrahydrofuran and the like. An acidacceptor such as excess amine or sodium carbonate is desirable and atemperature within the range of 25175 C. is preferred.

The compounds of this invention are physiologically active in thecentral nervous system. Some of the compounds such as3-(2-dimethylaminoethyl)-8-isopropyl-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one have antidepressant activity,while others such as 3-(2-dimethylaminoethyl) 1,3,4,5 tetra hydro 1,3benzodiazepin 2 one show CNS depressant activity.

The antidepressant properties of the compounds prepared by the processof the present invention are determined by measuring their ability tocounteract a depression induced in animals by the administration oftetrabenazine hexamate. Graded doses of the active compounds of thisinvention are administered to groups of mice, and this is followed byadministering a dose of tetrabenazine which is known to markedly depressthe exploratory behavior of normal mice. The antidepressant treatedgroups show normal exploratory behavior, while the control groups, andgroups treated with an ineffective antidepressant agent, do not showthis normal exploratory behavior, but show the well known profounddepression induced by tetrabenazine. The results from several doselevels are used to establish effective dose ranges. The anti-depressantcompounds prepared by the process of this invention show their desirableproperties by this procedure at dose levels which produce little or nountoward side effects.

The CNS depressant properties, such as hypnotic and muscle relaxant typeactivity is indicated by several procedures. For example, a test whichindicates hypnotic and/ or muscle relaxant type activity is representedby the following rod walking test. Groups of 6 mice each are tested fortheir ability to walk across a horizontal rod in a normal manner afterreceiving graded interperitoneal doses of a test compound. A medianeffective dose (RWD) is estimated.

A test which indicates tranquilizing activity is represented by ameasure of the reduction in motor activity. One-half this dose is givento a group of 5 mice and a 5 minute count of motor activity is recorded(actophotometer). Counts of 250 are considered to indicate a specificreduction (more than two standard deviations) of activity at a dosecausing only minimal impairment of neurological function as measured byrod Walking ability. Compounds that appeared to reduce motor activity 25count) are administered to additional groups of mice at graded doses andtested similarly. The dose (MDD) which causes a 50% reduction of motoractivity (a count of 250) is estimated.

As a test for toxicity or margin of safety, the compounds thatspecifically reduce motor activity are given to 10 mice at a dose of 10X(MDD). The compounds that did not reduce motor activity are given to 10mice at a dose of 4 (RWD). If more than 50% of the mice die within 24hours, the compound is rejected for reasons of toxicity or low margin ofsafety. If 50% of the mice die, the compound is considered for furtherstudy.

The compounds of the present invention for use as tranquilizers orantidepressants can be incorporated in various pharmaceutical forms suchas tablets, capsules. pills and so forth, for immediate or sustainedrelease, by combining with suitable carriers. The daily dose may varyfrom 10 mg. to 1000 mg. They may be in the form of dosage units forsingle therapeutic dose or in small units for multiple dosages or inlarger units for division into single doses. Obviously, in addition tothe therapeutic compound there may be present excipients, binders,fillers and other therapeutically inert ingredients necessary in theformulation of the desired pharmaceutical preparation.

The following specific examples illustrate the preparation ofrepresentative benzodiazepin-Z-ones and thiones of the presentinvention. Parts are by Weight unless otherwise indicated.

EXAMPLE 1 Preparation of3-(2-dimethylaminoethyl)-l,3,4,5-tetrahydro-ZH-l,3-benzodiazepin-2-one Asolution of 8.5 parts of N,N-carbonyldiimidazole in 70 parts oftetrahydrofuran is added to a solution of 9.0 parts ofo-nitrophenylacetic acid in 30 parts of tetrahydrofuran and the mixtureis stirred for 30 minutes. A solution of 4.8 parts ofN,N-dimethylethylenediamine in parts of tetrahydrofuran is added and themixture is stirred at C. for 90 minutes and then at reflux temperaturefor minutes. The reaction mixture is concentrated to remove the solventand the residue is warmed with 50 parts of warm water and extracted fourtimes with benzene. The benzene layers are combined, washed with alittle Water and concentrated. The residue crystallizes and is washedonto a filter with ether. The yield of N (2 dimethylaminoethyl) 2 (onitrophenyl)acetamide, melting point 76-78 C., is 64%.

A mixture of 10 parts of N-(Z-dimethylaminoethyl)-2-(o-nitrophenyl)acetamide (prepared above), parts of 1 N hydrochloricacid, 160 parts of ethanol and 1 part or' 10% paJladium-on-carboncatalyst is shaken in a Parr hydrogenator under about 3 atmospheres ofhydrogen pressure for 1 hour. The catalyst is filtered off and themother liquor is concentrated to remove the solvent. The residue isstirred with 30 parts of water and 10 parts of 5 N sodium hydroxide andthe mixture is extracted with benzene. The benzene extracts areconcentrated and 6.8 parts of pink crystals, melting point 93-95 C., areobtained.

The above material, N-(Z-dimethylaminoethyl)-2-(oaminophenyl)acetamide,is dissolved in parts of tetrahydrofuran and added dropwise to parts byvolume of a cooled solution of 1 molar borane in tetrahydrofuran. Themixture is left at room temperature for 20 hours and then heated atreflux temperature for one hour. The mixture is cooled and 25 parts of 5N hydrochloric acid are carefully added. The tetrahydrofuran isdistilled off and 15 parts of sodium hydroxide are carefully added tothe remaining reaction mixture. This mixture is extracted with benzeneand the benzene layer is Washed with water and then concentrated. TheN-(o-aminophenethyl)-N',N-dimethylethylenedamine is obtained as aviscous oil.

A solution of 5.2 parts of the above oil in 50 parts of benzene iscooled and a solution of 4.8 parts of N,N-carbonyldiimidazole in 50parts of tetrahydrofuran is added. The solution is allowed to stand atroom temperature for 20 hours, heated on the steam bath for 2 hours, andconcentrated to remove the solvent. The residue is diluted with 40 partsof water and the product is extracted into benzene. The benzene layer iswashed with a little water and concentrated. The residue is trituratedwith a little ether and filtered and the crystalline product isrecrystallized from ethyl acetate. The 3-(2-dimethylaminoethyl)-l,3,4,5-tetrahydro-2H-1,3-benzodiazepin 2 one melts at 1141l6 C.

When the above compound is dissolved in benzene and treated withalcoholic hydrogen chloride, the hydrochloride salt precipitates. Thisproduct melts at 23l233 C. after recrystallization from ethanol. Thiscompound has (CNS) depressant properties.

EXAMPLE 2 Preparation of 3-(2-pyrrolidinoethyl)-l,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one hydrochloride When the sequence of reactionsdescribed in Example 1 is carried out, starting with o-nitrophenylacetic acid and 1-(2-aminoethyl)pyrrolidine, the above compound, meltingpoint 225227 C., is obtained. This compound has CNS depressantproperties. The above hydrochloride is dissolved in water, sodiumhydroxide added and the base compound extracted with benzene.

EXAMPLE 3 Preparation of 3-(2-dimethylaminoethyl)-8-isopropyl-l,3,

4,5 tetrahydro-ZH-1,3-benzodiazepin 2 one hydrochloride When4-isopropyl-Z-nitrophenylacetic acid is substituted foro-nitrophenylacetic acid in the procedure of Example 1, the abovecompound, melting point 2l52l7 C. is obtained. This compound is activeas an anti-depressant. The above hydrochloride is dissolved in water,sodium hydroxide added and the base compound extracted with benzene.

EXAMPLE 4 Preparation of 8-chlor0-3-(Z-dimethylaminoethyl-l,3,4,5-tetrahydro-2H-1,3 -benzodiazepin-2-one A mixture of 3.9 parts of2-(4-chloro-2-nitrophenyl)-N- (Z-dimethylaminoethyl)acetamide, 2.1 partsof iron powder, 3.2 parts of 5 N hydrochloric acid, and 7.0 parts of 70%ethanol is heated, under nitrogen, at reflux temperature for 45 minutes.The reaction mixture is cooled, diluted with 15 parts of 50% ethanol andfiltered. The precipitate is washed with 15 parts of 50% ethanol. Themother liquors are diluted With 50 parts of Water and concentrated untilthe ethanol is removed. The mixture is filtered to remove some insolublematerial and the filtrate is treated with 5 parts of 5 N sodiumhydroxide and extracted with benzene. The benzene layer is washed withwater, dried over magnesium sulfate and concentrated. The crystallineresidue is triturated with ether and filtered. The 2 (2-amino 4chlorophenyl)-N-(Z-dimethylaminoethyl)acetamide melts at 8990 C.

A solution of 2.6 parts of 2-(2-amino-4-chlorophenyl)-N-(Z-dimethylaminoethyl)acetamide in 20 parts of tetra hydrofuran isadded dropwise, with stirring and under nitrogen, to 30 parts of 1 molarborane in tetrahydrofuran. The mixture is stirred for 30 minutes, leftovernight at room temperature and then heated at reflux temperature forone hour. The mixture is cooled and parts of 5 N hydrochloric acid iscarefully added. The tetrahydrofuran is distilled off and 6 parts ofsodium hydroxide pellets are carefully added. The mixture is extractedwith benzene and the benzene layer is washed with water, dried overmagnesium sulfate and concentrated. The N-[2-(2-amino- 4chlorophenyl)ethyl] N,N' dimethylethylenediamine is obtained as an oilin nearly quantitative yield.

A solution of 2.4 parts ofN-[2-(2-amino-4-chlorophenyl)ethyl]-N,N'-dimethylethylenediamine in 20parts of tetrahydrofuran is cooled and 1.9 parts of 92% N',N'-carbonyldiimidazole in 30 parts of tetrahydrofuran are added. Thesolution is left at room temperature for 3 days and then heated on thesteam bath for 4 hours. The mixture is concentrated to remove thesolvent, warmed with 50 parts of water and filtered. The product,8-chloro-3-(2- dimethylaminoethyl) 1,3,4,5 tetrahydro 2H 1,3benzodiazepin-2-one melts at 148l50 C. The hydrochloride salt melts at256258 C.

6 EXAMPLE 5 Preparation of 6-chloro-3-(2-dimethylaminoethyl)-l,3,4,5-tetrahydro-2H-1,3 -benzodiazepin-2-one When 2- 6-chloro-2-nitrophenyl)-N- (2-dimethylaminoethyl) acetamide is substituted for 2 (4 chloro 2nitrophenyl)-N-(Z-dimethylarninoethyl) acetamide in the procedure ofExample 4, the above compound, melting point 173l75 C. is obtained.

EXAMPLE 6 Preparation of S-chloro-3-(2-pyrrol-idinoethyl)-1,3,4,5-tetrahydro-2H-l,3 -benzodiazepin-2-one The above compound is obtainedwhen 2-(4-chl0ro-2- nitrophenyl)-N-(Z pyrrolidinoethyl)acetamide issubstituted for 2 (4 chloro 2 nitrophenyl) N (2dimethylaminoethyl)acetamide in the procedure of Example'4.

EXAMPLE 7 Preparation of 8-bromo 3 (Z-dimethylaminoethyl)-6-methyl-l,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one If 2 (4 bromo 6methyl 2 nitrophenyl) N (2dimethylaminoethyl)acetamide is substitutedfor 2-(4- chloro 2 nitrophenyl) N (2 dimethylaminoethyl) acetamide inthe procedure of Example 4, the above compound is obtained.

EXAMPLE 8 Preparation of 6,8-dichloro-3-(2-dimethylaminoethyl)-l,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one When 2 (4,6 dichloro 2nitrophenyl) N (2- dimethylaminoethyl)acetamide is substituted for 2-(4-chloro 2 nitrophenyl) N (2 dimethylaminoethyl) acetamide in theprocedure of Example 4, the above compound is obtained.

EXAMPLE 9 Preparation of 3- (Z-piperidinoethyl -1,3,4,5-tetrahydro-S-trifiuoromethyl-ZH-l,3-benzodiazepin-2-one The above compound isobtained when 2-nitro-4-trifluoromethylphenylacetic acid is substitutedfor o-nitrophenylacetic acid and 1-(2-aminoethyl)piperidine issubstituted for N,N-dimethylethylenediamine in the procedure of Example1.

EXAMPLE 11 Preparation of 3-(4-dimethylaminobutyl)-8-methoxy-1,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one The above compound is obtainedwhen o-nitrophenyl acetic acid is replaced by4-methoxy-2-nitrophenylacetic acid and N,N-dimethylethylenediamine isreplaced by 4- dimethylaminobutylamine in the procedure of Example 1.

EXAMPLE 12 Preparation of 3-(2-dimethylaminoethyl)-8-methyl-1,3,4,S-tetrahydro-ZH-1,3-benzodiazepin-2-one This compound is obtained when4-methyl-2-nitrophenylacetic acid is used in place ofo-nitrophenylacetic acid in the procedure of Example 1.

EXAMPLE 13 Preparation of 1-ethyl-3-(Z-dimethylaminoethyl)-1,3,4,5-tetrahydro-ZH-1,3-benzodiazepin-2-one If N [o (ethylamino)phenethyl]N,N' dimethylethylenediamine is treated with N,N-carbonyldiimidazole 7by the procedure of Example 1, this compound is obtained.

EXAMPLE 14 Preparation of3-(2-benzylmethylaminoethyl)-1,3,4,5-tetrahydro-ZH-1,3-benzodiazepin-2-oneThe above compound is obtained if N-(o-aminophenethyl)-N benzyl Nmethylethylenediamine is treated with N,N-carbonyl diimidazole asdescribed in Example 1.

EXAMPLE 15 Preparation of3-(2-methylaminoethyl)-1,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one Amixture of 10 parts of 3-(2-benzylmethylaminoethyl) 1,3,4,5 tetrahydro1,3 benzodiazepin 2 one, 150 parts of ethanol and 1 part of 10%palladiumon-carbon catalyst is shaken in a Parr hydrogenator under about45 pounds of hydrogen pressure until reduction is complete. The catalystis filtered off and the mother liquor is concentrated to recover the3-(2-methylarninoethyl) 1,3,4,5 tetrahydro 1,3 benzodiazepin 2- one.

EXAMPLE 16 Preparation of 3-(Z-metbylcyclohexylaminoethyl)-1,3,4,S-tetrahydro-ZH-1,3-benzodiazepin-2-one This compound is obtained whenN-methyl-N-cyclohexylethylenediamine is substituted forN,N-dimethylenediamine in the procedure of Example 1.

EXAMPLE 17 Preparation of 3 [2 methyl(cyclopropylmethy1)aminoethyl]1,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one When N methyl N(cyclopropylmethyl)ethylenediamine is substituted forN,N-dimethylethylenediamine in the procedure of Example 1, this compoundis obtained.

EXAMPLE 18 Preparation of 3[2-(4-methylpiperidino)ethyl]-l,3,4,5-

tetrahydro-2H-1,3-benzodiazepin-2-one If1-(2-aminoethyl)-4-methylpiperidine is substituted forN,N-dimethylethylenediamine in the procedure of Example 1, this compoundis obtained.

EXAMPLE 19 Preparation of 3-[2-(3-methyl-1-pyrrolidinyl)ethyl]-l,3,4,5-tetrahydro-2H-l,3benzodiazepin-2-one This compound is obtained whenl-(2-aminoethyl)-3- methylpyrrolidine is substituted forN,N-dimethylethylenediamine in the procedure of Example 1.

EXAMPLE 20 Preparation of 3-[2-(2,6-dimethylmorpholino)ethyl]1,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one If4-(2-aminoethyl)-2,6-dimethy1morpholine is substituted forN,N-dimethylethylenediamine in the procedure of Example 1, this compoundis obtained.

EXAMPLE 21 Preparation of 3-[2-hexamethyleneiminoethyl] l,3,4,5-tetrahydro-ZH-l,3-benzodiazepin-2-one When1-(2-aminoethyl)hexamethyleneimine is used in place ofN,N-dimethylethylenediamine in the procedure of Example 1, this compoundis obtained.

EXAMPLE 22 Preparation of 3-[2-(azabicyclo[3.2.2]nonan-3-yl)ethyl]-1,3,4,S-tetrahydro-ZH-1,3-benzodiazepin-2-one The above compound isobtained when the N,N-dimethylethylenediamine is replaced by3-(2-aminoethyl) azabicyclo[3.2.2]-nonane in the procedure of Example 1.

8 EXAMPLE 23 Preparation of 3-[2-(4-phenylpiperidino)ethyl]-1,3,4,5-tetrahydro-ZH-1,3-benzodiazepin-2-one If1-(2-aminoethyl)-4-phenylpiperidine is used in place ofN,N-dimethylethylenediamine, the above compound is obtained.

EXAMPLE 24 Preparation of 3-[2-(4-ethyl-1-piperazinyl)ethy1]-1,3,4,5-tetrahydro-ZH-1,3-benzodiazepin-2-one When1-(2-aminoethyl)-4-ethylpiperazine is substituted forN,N-dimethylethylenediamine in the procedure of Example 1, the abovecompound is prepared.

EXAMPLE 25 Preparation of 3-[2-(4-benzyl-1-piperazinyl)ethyl]-l,3,4.5-tetrahydro-2H-1,3-benzodiazepin-2-one The above compound is obtainedwhen 1-benzyl-4-[2- (o-aminophenethylamino)ethyl]piperazine is treatedwith N,N-carbonyldiimidazole as described in Example 1.

EXAMPLE 26 Preparation of3[2-(l-piperazinyDethyl]1,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-oneWhen 3 [2 (4 benzyl 1 piperazinyl)ethyl] .l.3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one is reduced by the procedureof Example 15, the above compound is obtained.

EXAMPLE 27 Preparation of 3-[2-(4-phenyl-1-piperazinyl)ethyl]-1,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2one If1-(2-aminoethyl)-4-phenylpiperazine is substituted forN,N-dimethylethylenediamine in the procedure of Example 1, this compoundis obtained.

EXAMPLE 28 Preparation of 3 [2 (4 p chlorophenyl 1 piperazinyl)ethyl]1,3,4,5 tetrahydro-2H 1,3-benzodiazepin-Z-one This compound is obtainedwhen 1-(p-chlorophenyl)- 4-[2-(o-aminophenethylamino)ethyl]piperazine istreated with N,N-carbonyldiimidazole as described in Example 1.

EXAMPLE 29 Preparation of 3-[2-(4-p-ethylphenyl-1-piperazinyl)ethyl]-1,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one When1-(Z-aminoethyl)-4-p-ethylphenylpiperazine is substituted forN,N-dimethylethylenediamine in the procedure of Example 1, this compoundis obtained.

EXAMPLE 30 9 ethylarnino)ethyl]-4-phenyl-l,2,3,5 tetrahydropyridine istreated with N,N-carbonyldiirnidazole as described in Example 1.

EXAMPLE 33 reparation of 3-[2-(3,6dihydro-4rn-tolyl-1(2H)-pyridyl)ethyl] 1,3,4,5tetrahydro-2H-1,3-benzodiazepin- 2-one When1-[2-(o-aminophenethylamino)ethyl]-4-rn-tolyl-1,2,5,6-tetrahydropyridine and N,N-carbonyldiirnidaz0le are reacted asdescribed in Example 1, the above compound is obtained.

EXAMPLE 34 Freparation of 3 [2 (4 p-chlorophenyl-3,6-dihydro- 1(21-1)pyridyl)ethyl] 1,3,4,5 tetrahydro 2H-l,3- benzodiazepin-Z-one If 4 pchlorophenyl-l-[2-(o-aminophenethylamino)ethyl]-1,2,5,6-tetrahydropyridine is treated with N,N'-

carbonyldiirnidazole as described in Example 1, the above compound isprepared.

EXAMPLE 35 Preparation of 3-[2-(4-p-chlorophenylpiperidino)ethyl]-1,3,4,5-tetrahydro-2H-1,3-benzodiaZepin-2-one This compound is obtainedwhen 4-(p-chlorophenyD-1- [2-(o-aminophenethylamino)ethyl]piperidine istreated with N,N-carbonyldiimidazole as described in Example 1.

I claim:

1. A benzodiazepin-Z-one of the formula:

piperazinyl, 4-lower alkyl-l-piperazinyl, 4-benzyl-1-piperazinyl,4-phenyl-1-piperazinyl, 4-(lower alkoxyphenyl)-lpiperazinyl,4-trifiuoromethylphenyl 1 piperazinyl, 4-(loweralkylphenyl)-l-piperazinyl, 4 halophenyl-l-piper- :azinyl,3,6-dihydro-4-phenyl-1(2H)-pyridyl, 4-loweralkylphenyl 3,6dihydro-1(2H)pyridyl, 3,6-dihydro-4-halophenyl-1(2H)pyridyl, andazabicyclo[3.2.2]nonan-3-yl; and acid addition salts thereof.

2. A benzodiazepin-Z-one according to claim 1: 3-(2-diloweralkylaminoethyl) 1,3,4,5 tetrahydro 2H 1,3- benzodiazepin-Z-one.

3. The benzodiazepin-Z-one according to claim 11: 3-(2-dimethylaminoethyl) l,3,4,5 tetrahydro 2H 1,3- benzodiazepin-2-one.

4. The benzodiazepin-Z-one according to claim 1: 3-(2- pyrrolidinoethyl)1,3,4,5 tetrahydro 2H 1,3 benzodiazepin-Z-one.

5. The benzodiazepin-Z-one according to claim 1: 3-(2-dimethylaminoethyl) 8 isopropyl 1,3,4,5-tetrahydro-2H-1,3-benzodiazepin-2-one.

6. The benzodiazepin-Z-one according to claim 1: 8- chloro 3 (2dimethylaminoethyl)-1,3,4,5-tetrahydro- 2H-1,3-benzodiaZepin-2-one.

7. The benzodiazepin-Z-one according to claim 1: 6- chloro 3 (2dimethylaminoethyl)-1,3,4,5-tetrahydro 2H-1,3-benzodiazepin-2-one.

8. The benzodiazepin-Z-one according to claim 1: 8- chloro 3 (2pyrrolidinoethyl)-1,3,4,5-tetrahydro-2H- 1,3-benzodiazepin-2-one.

9. The benzodiazepinQ-one according to claim 1: 3-(2- dimethylaminoethyl) 8 methyl-1,3,4,5-tetrahydro-2H- 2H-1,3-benzodiazepin-2-one.

10. The benzodiazepin-Z-one according to claim It: 3- (2benzylmethylaminoethyl) 1,3,4,5-tetrahydro 2H- 1,3-benzodiazepin-2-one.

References Cited UNITED STATES PATENTS 3,414,563 12/1968 Griot 260-2393HENRY R. JILES, Primary Examiner R. T. BOND, Assistant Examiner US. Cl.X.R.

